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造血细胞移植后,唾液白消安是口腔黏膜炎及唾液抗氧化酶变化的原因吗?

Is Salivary Busulfan the Cause of Oral Mucositis and the Changes in Salivary Antioxidant Enzymes After Hematopoietic Cell Transplantation?

作者信息

de Paula Eduardo Fernanda, Bezinelli Letícia Mello, Carvalho Danielle L C, Ferreira Mariana Henriques, Gobbi Marcella, Rosin Flavia C P, Dos Santos Ferreira Carlos Eduardo, Sodre da Costa Lidiane Soares, Hamerschlak Nelson, Corrêa Luciana

机构信息

Bone Marrow Transplantation Unit, Hospital Israelita Albert Einstein; and.

Pathology Department, School of Dentistry, University of São Paulo, São Paulo, Brazil.

出版信息

Ther Drug Monit. 2020 Aug;42(4):565-571. doi: 10.1097/FTD.0000000000000757.

DOI:10.1097/FTD.0000000000000757
PMID:32205679
Abstract

BACKGROUND

To determine whether the busulfan (Bu) present in saliva during hematopoietic cell transplantation (HCT) conditioning correlates with oral mucositis and the changes in salivary antioxidant enzymes.

METHODS

Bu levels in the plasma and saliva of 19 patients who received HCTs were quantified. Salivary flow and salivary superoxide dismutase and catalase activities were measured during HCT. For the toxicity analysis of salivary Bu, an in vitro assay was conducted by exposing human keratinocytes to artificial saliva containing Bu.

RESULTS

Plasma and salivary Bu concentrations were very similar (rho = 0.92, P < 0.001). Salivary Bu concentration correlated with the degree of oral mucositis severity (rho = 0.391, P = 0.029) and was inversely proportional to salivary superoxide dismutase and catalase activities (rho = -0.458, P = 0.036; rho = -0.424, P = 0.043, respectively). Cells exposed to Bu-containing saliva had fewer viable cells (P < 0.01) and more apoptotic cells (P = 0.001) than those exposed to non-Bu-containing saliva.

CONCLUSIONS

Bu found in saliva during HCT conditioning was correlated with severe oral mucositis and the reduction in salivary antioxidative activity. Furthermore, Bu can be toxic to keratinocytes.

摘要

背景

确定造血细胞移植(HCT)预处理期间唾液中白消安(Bu)水平是否与口腔黏膜炎及唾液抗氧化酶变化相关。

方法

对19例接受HCT的患者血浆和唾液中的Bu水平进行定量分析。在HCT期间测量唾液流量以及唾液中超氧化物歧化酶和过氧化氢酶的活性。为分析唾液中Bu的毒性,通过将人角质形成细胞暴露于含Bu的人工唾液中进行体外试验。

结果

血浆和唾液中Bu浓度非常相似(rho = 0.92,P < 0.001)。唾液中Bu浓度与口腔黏膜炎严重程度相关(rho = 0.391,P = 0.029),且与唾液中超氧化物歧化酶和过氧化氢酶活性呈负相关(分别为rho = -0.458,P = 0.036;rho = -0.424,P = 0.043)。与暴露于不含Bu的唾液中的细胞相比,暴露于含Bu唾液中的细胞活细胞数量更少(P < 0.01),凋亡细胞数量更多(P = 0.001)。

结论

HCT预处理期间唾液中的Bu与严重口腔黏膜炎及唾液抗氧化活性降低相关。此外,Bu对角质形成细胞具有毒性。

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